Correspondence AIDS 2014, 28:1537–1543
Research on oral pre-exposure prophylaxis in sub-Saharan Africa is an example of biomedical tunnel vision ‘A technical solution may be defined as one that requires a change only in the techniques of the natural sciences, demanding little or nothing in the way of change in human values or ideas of morality.’ –Garrett Hardin (1968) [1]
I read with interest the Opinion piece by Cowan and Macklin [2], which concluded: ‘pre-exposure prophylaxis [is] ready for prime time use in HIV prevention research’. Presumably, this prime time research will occur in subSaharan Africa, where several trials of oral pre-exposure prophylaxis (PreP) have already failed in high-risk women [3,4]. The enthusiasm surrounding PreP highlights the current paradigm for HIV prevention: namely, that we will treat our way out of the pandemic. The idea of chemoprophylaxis is problematic on many levels, but mainly stems from our attempts to ‘force nature into the conceptual boxes supplied by [our] professional education’ [5]. Here, I am speaking mainly to clinical researchers, public health professionals, and other specialists in the biomedical paradigm. Despite growing opinion that oral PreP will not likely be efficacious outside the research arena [6], our incremental efforts to gain a couple of extra percent of prevention at the cost of medicalizing a disease-free state gloss over the structural drivers of generalized epidemics. This type of approach shapes society’s view that the problem of HIV prevention is one that has been handed over to the scientists and that we will find a solution. In other words, legitimation of the biomedical approach – in this case chemoprophylaxis – ‘gives a normative dignity to its practical imperatives’ [7]. Or, better yet, the expectation of a biomedical solution shapes the way we see the phenomena on which we are trying to intervene. Consider the following social psychology experiment: individuals were shown a deck of cards in which the color of certain cards was exchanged for its opposite (e.g. an individual might be shown a black queen of hearts). The individuals would consistently identify the card as belonging to suit (i.e. as a queen of spades in the previous example.) After repeated trials and a growing sense of uncertainty, the individuals (in general) would finally recognize the anomaly [8]. Analogously, we live in a world where health policy makers and research funders (e.g. Gates Foundation) increasingly demand technical solutions to the issues of public health. Just like the
expectation of a standard deck precludes our seeing a black queen of hearts, technocratic lenses preclude us from seeing societal factors as determinants of disease. Only a radical unsettling of our biomedical tunnel vision will provide the mobilization necessary to break free from the fetish for technical (and chemical) solutions – an unsettling which recognizes that the penchant for magic bullets is sometimes misplaced – an unsettling which helps policy makers and citizens alike realize that meaningful social interventions (e.g. abolishing school fees for girls, ‘real’ enforcement of domestic violence laws, affirmative action for increased participation in the labor market, banning child marriage, etc.) will likely provide better prevention then pills or microbicides.
Acknowledgements Conflicts of interest There are no conflicts of interest. Eugene T. Richardsona,b, aDivision of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, and bDepartment of Anthropology, Stanford University, Stanford, California, USA. Correspondence to Dr Eugene T. Richardson, Division of Infectious Diseases and Geographic Medicine, 300 Pasteur Road, Lane Building, L134, Stanford, CA 94305-5107, USA. E-mail: [email protected] Received: 1 February 2014; revised: 6 February 2014; accepted: 6 February 2014.
References 1. Hardin G. The Tragedy of the Commons. Science 1968; 162:1243–1248. 2. Cowan EA, Macklin R. Is preexposure prophylaxis ready for prime time use in HIV prevention research? AIDS 2014; 28:293– 295. 3. Van Damme L, Corneli A, Ahmed K, Agot K. Preexposure prophylaxis for HIV infection among African women. N Engl J Med 2012; 367:411–422. 4. Marrazzo JM, Ramjee G, Nair G, Palanee T. Pre-exposure prophylaxis for HIV in women: daily oral tenofovir, oral tenofovir/ emtricitabine or vaginal tenofovir gel in the VOICE study (MTN 003). 20th Conf Retroviruses Opportunistic Infect Atlanta [Abstr 26LB 2013].
ISSN 0269-9370 Q 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
1537
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
1538
AIDS
2014, Vol 28 No 10
5. Kuhn TS. The structure of scientific revolutions. 3rd ed. Chicago: University of Chicago Press; 1996. 6. Roberts ET, Matthews DD. HIV and chemoprophylaxis, the importance of considering social structures alongside biomedical and behavioral intervention. Soc Sci Med 2012; 75:1555– 1561.
7. Berger PL, Luckmann T. The social construction of reality: a .treatise in the sociology of knowledge. New York: Anchor; 1967 8. Bruner JS, Postman L. On the perception of incongruity: a paradigm. J Pers 1949; 18:206–223.
DOI:10.1097/QAD.0000000000000256
Acute renal failure and liver toxicity in an HIV/hepatitis C coinfected patient receiving telaprevir and boosted atazanavir Despite the potential benefit of telaprevir (TVR) in HIV/ hepatitis C virus (HCV)-coinfected patients, there is a concern about possible clinically significant antiretroviral drug interactions, and real-life experience in this clinical setting is lacking. We report the case of a 51-year-old HIV/HCVcoinfected patient receiving tenofovir (TDF), emtricitabine, and ritonavir-boosted atazanavir (ATVr), who started therapy with TVR and developed acute renal failure and liver toxicity. The patient had been on stable TDF therapy for 2 years. A few weeks after starting TVR, the patient experienced a progressive deterioration in renal function (Table 1). At week 2, TDF/emtricitabine was changed to abacavir/lamivudine to avoid TDFrelated nephrotoxicity. At week 4, the patient was hospitalized for severe nausea vomits and dehydration. Hepatic function was abnormally elevated, with no apparent explanation. ATVoverexposure was suspected as the cause of liver injury, and ATV plasma concentration was found to be abnormally elevated (2.7 mg/ml) at 60 h after the last dose. HCV double therapy was reintroduced on the fifth day of hospitalization, and both HIV and HCV viral loads remained undetectable at week 12.
In the clinical setting, a significant estimated glomerular filtration rate decrease during TVR treatment was recently reported, particularly in patients with risk factors for renal impairment [1,2]. TVR has shown invitro inhibition of drug transporters expressed in the kidney [3]. The inhibition of organic cation transporter 2 (OCT2) by telaprevir has been suggested as the mechanism responsible for elevations in plasma creatinine during TVR therapy [4], and this may have contributed to the initial rise on creatinine plasma level in our patient. Tenofovir has been clearly related to renal toxicity, mainly because of tubular dysfunction. The combination of ATV and TDF results in an increase in TDF exposure that could lead to a higher risk of nephrotoxicity [5]. Several antiretroviral drugs have proven to be substrates of OCT1 and OCT2, which suggests that drug interactions related to the OCTs may be relevant for antiretroviral therapy, in particular, by affecting hepatic or renal elimination [6]. In this line, this journal has recently published the case of a patient on TDF-based regimen who suffered rapid deterioration of renal function after starting TVR and presented increased TDF plasma trough concentrations
Table 1. Laboratory findings.
Hemoglobin (mg/dl) White blood cells (10E6/l) Neutrophils (10E6//l) Platelets (10E6/l) CD4þ cells [n (%)] HIV-RNA (IU/ml) HCV-RNA (IU/ml) Plasma creatinine (mg/dl) eGFR (ml/min) Urine analysis ALT (IU/l) AST (IU/l) GGT (IU/l) Alkaline phosphatase (IU/l) Total bilirubin (mg/dl) Direct bilirubin (mg/dl)
TDF initiationa
TVR initiationb
Week 2c
Week 3
Week 4d
14.3 4600 2200 158 000 85 (5%) 43 871
13.8 3900 1400 110 000
12.5 3200 1200 131 000
12.3 3800 2000 146 000
0.86 78.6 Neg 55.7
15.2 4900 1900 167 000 420 (10%)
Research on oral pre-exposure prophylaxis in sub-Saharan Africa is an example of biomedical tunnel vision ‘A technical solution may be defined as one that requires a change only in the techniques of the natural sciences, demanding little or nothing in the way of change in human values or ideas of morality.’ –Garrett Hardin (1968) [1]
I read with interest the Opinion piece by Cowan and Macklin [2], which concluded: ‘pre-exposure prophylaxis [is] ready for prime time use in HIV prevention research’. Presumably, this prime time research will occur in subSaharan Africa, where several trials of oral pre-exposure prophylaxis (PreP) have already failed in high-risk women [3,4]. The enthusiasm surrounding PreP highlights the current paradigm for HIV prevention: namely, that we will treat our way out of the pandemic. The idea of chemoprophylaxis is problematic on many levels, but mainly stems from our attempts to ‘force nature into the conceptual boxes supplied by [our] professional education’ [5]. Here, I am speaking mainly to clinical researchers, public health professionals, and other specialists in the biomedical paradigm. Despite growing opinion that oral PreP will not likely be efficacious outside the research arena [6], our incremental efforts to gain a couple of extra percent of prevention at the cost of medicalizing a disease-free state gloss over the structural drivers of generalized epidemics. This type of approach shapes society’s view that the problem of HIV prevention is one that has been handed over to the scientists and that we will find a solution. In other words, legitimation of the biomedical approach – in this case chemoprophylaxis – ‘gives a normative dignity to its practical imperatives’ [7]. Or, better yet, the expectation of a biomedical solution shapes the way we see the phenomena on which we are trying to intervene. Consider the following social psychology experiment: individuals were shown a deck of cards in which the color of certain cards was exchanged for its opposite (e.g. an individual might be shown a black queen of hearts). The individuals would consistently identify the card as belonging to suit (i.e. as a queen of spades in the previous example.) After repeated trials and a growing sense of uncertainty, the individuals (in general) would finally recognize the anomaly [8]. Analogously, we live in a world where health policy makers and research funders (e.g. Gates Foundation) increasingly demand technical solutions to the issues of public health. Just like the
expectation of a standard deck precludes our seeing a black queen of hearts, technocratic lenses preclude us from seeing societal factors as determinants of disease. Only a radical unsettling of our biomedical tunnel vision will provide the mobilization necessary to break free from the fetish for technical (and chemical) solutions – an unsettling which recognizes that the penchant for magic bullets is sometimes misplaced – an unsettling which helps policy makers and citizens alike realize that meaningful social interventions (e.g. abolishing school fees for girls, ‘real’ enforcement of domestic violence laws, affirmative action for increased participation in the labor market, banning child marriage, etc.) will likely provide better prevention then pills or microbicides.
Acknowledgements Conflicts of interest There are no conflicts of interest. Eugene T. Richardsona,b, aDivision of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, and bDepartment of Anthropology, Stanford University, Stanford, California, USA. Correspondence to Dr Eugene T. Richardson, Division of Infectious Diseases and Geographic Medicine, 300 Pasteur Road, Lane Building, L134, Stanford, CA 94305-5107, USA. E-mail: [email protected] Received: 1 February 2014; revised: 6 February 2014; accepted: 6 February 2014.
References 1. Hardin G. The Tragedy of the Commons. Science 1968; 162:1243–1248. 2. Cowan EA, Macklin R. Is preexposure prophylaxis ready for prime time use in HIV prevention research? AIDS 2014; 28:293– 295. 3. Van Damme L, Corneli A, Ahmed K, Agot K. Preexposure prophylaxis for HIV infection among African women. N Engl J Med 2012; 367:411–422. 4. Marrazzo JM, Ramjee G, Nair G, Palanee T. Pre-exposure prophylaxis for HIV in women: daily oral tenofovir, oral tenofovir/ emtricitabine or vaginal tenofovir gel in the VOICE study (MTN 003). 20th Conf Retroviruses Opportunistic Infect Atlanta [Abstr 26LB 2013].
ISSN 0269-9370 Q 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
1537
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
1538
AIDS
2014, Vol 28 No 10
5. Kuhn TS. The structure of scientific revolutions. 3rd ed. Chicago: University of Chicago Press; 1996. 6. Roberts ET, Matthews DD. HIV and chemoprophylaxis, the importance of considering social structures alongside biomedical and behavioral intervention. Soc Sci Med 2012; 75:1555– 1561.
7. Berger PL, Luckmann T. The social construction of reality: a .treatise in the sociology of knowledge. New York: Anchor; 1967 8. Bruner JS, Postman L. On the perception of incongruity: a paradigm. J Pers 1949; 18:206–223.
DOI:10.1097/QAD.0000000000000256
Acute renal failure and liver toxicity in an HIV/hepatitis C coinfected patient receiving telaprevir and boosted atazanavir Despite the potential benefit of telaprevir (TVR) in HIV/ hepatitis C virus (HCV)-coinfected patients, there is a concern about possible clinically significant antiretroviral drug interactions, and real-life experience in this clinical setting is lacking. We report the case of a 51-year-old HIV/HCVcoinfected patient receiving tenofovir (TDF), emtricitabine, and ritonavir-boosted atazanavir (ATVr), who started therapy with TVR and developed acute renal failure and liver toxicity. The patient had been on stable TDF therapy for 2 years. A few weeks after starting TVR, the patient experienced a progressive deterioration in renal function (Table 1). At week 2, TDF/emtricitabine was changed to abacavir/lamivudine to avoid TDFrelated nephrotoxicity. At week 4, the patient was hospitalized for severe nausea vomits and dehydration. Hepatic function was abnormally elevated, with no apparent explanation. ATVoverexposure was suspected as the cause of liver injury, and ATV plasma concentration was found to be abnormally elevated (2.7 mg/ml) at 60 h after the last dose. HCV double therapy was reintroduced on the fifth day of hospitalization, and both HIV and HCV viral loads remained undetectable at week 12.
In the clinical setting, a significant estimated glomerular filtration rate decrease during TVR treatment was recently reported, particularly in patients with risk factors for renal impairment [1,2]. TVR has shown invitro inhibition of drug transporters expressed in the kidney [3]. The inhibition of organic cation transporter 2 (OCT2) by telaprevir has been suggested as the mechanism responsible for elevations in plasma creatinine during TVR therapy [4], and this may have contributed to the initial rise on creatinine plasma level in our patient. Tenofovir has been clearly related to renal toxicity, mainly because of tubular dysfunction. The combination of ATV and TDF results in an increase in TDF exposure that could lead to a higher risk of nephrotoxicity [5]. Several antiretroviral drugs have proven to be substrates of OCT1 and OCT2, which suggests that drug interactions related to the OCTs may be relevant for antiretroviral therapy, in particular, by affecting hepatic or renal elimination [6]. In this line, this journal has recently published the case of a patient on TDF-based regimen who suffered rapid deterioration of renal function after starting TVR and presented increased TDF plasma trough concentrations
Table 1. Laboratory findings.
Hemoglobin (mg/dl) White blood cells (10E6/l) Neutrophils (10E6//l) Platelets (10E6/l) CD4þ cells [n (%)] HIV-RNA (IU/ml) HCV-RNA (IU/ml) Plasma creatinine (mg/dl) eGFR (ml/min) Urine analysis ALT (IU/l) AST (IU/l) GGT (IU/l) Alkaline phosphatase (IU/l) Total bilirubin (mg/dl) Direct bilirubin (mg/dl)
TDF initiationa
TVR initiationb
Week 2c
Week 3
Week 4d
14.3 4600 2200 158 000 85 (5%) 43 871
13.8 3900 1400 110 000
12.5 3200 1200 131 000
12.3 3800 2000 146 000
0.86 78.6 Neg 55.7
15.2 4900 1900 167 000 420 (10%)
